tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2020 Jul 21;1-36.
doi: 10.1080/22221751.2020.1799723. Online ahead of print.
Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells
Sofia Appelberg[SUP] 1 [/SUP], Soham Gupta[SUP] 2 [/SUP], Sara Svensson Akusj?rvi[SUP] 2 [/SUP], Anoop T Ambikan[SUP] 2 [/SUP], Flora Mikaeloff[SUP] 2 [/SUP], Elisa Saccon[SUP] 2 [/SUP], ?kos V?gv?ri[SUP] 3 [/SUP], Rui Benfeitas[SUP] 4 [/SUP], Maike Sperk[SUP] 2 [/SUP], Marie St?hlberg[SUP] 3 [/SUP], Shuba Krishnan[SUP] 2 [/SUP], Kamal Singh[SUP] 2 5 [/SUP], Josef M Penninger[SUP] 6 7 [/SUP], Ali Mirazimi[SUP] 1 2 8 [/SUP], Ujjwal Neogi[SUP] 2 5 [/SUP]
Affiliations
Abstract
How severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections engage cellular host pathways and innate immunity in infected cells remains largely elusive. We performed an integrative proteo-transcriptomics analysis in SARS-CoV-2 infected Huh7 cells to map the cellular response to the invading virus over time. We identified four pathways, ErbB, HIF-1, mTOR and TNF signaling, among others that were markedly modulated during the course of the SARS-CoV-2 infection in vitro. Western blot validation of the downstream effector molecules of these pathways revealed a dose-dependent activation of Akt, mTOR, S6K1 and 4E-BP1 at 24 hours post infection (hpi). However, we found a significant inhibition of HIF-1α through 24hpi and 48hpi of the infection, suggesting a crosstalk between the SARS-CoV-2 and the Akt/mTOR/HIF-1 signaling pathways. Inhibition of the mTOR signaling pathway using Akt inhibitor MK-2206 showed a significant reduction in virus production. Further investigations are required to better understand the molecular sequelae in order to guide potential therapy in the management of severe coronavirus disease 2019 (COVID-19) patients.
Keywords: SARS-CoV-2; mTOR; proteomics; transcriptomics.
. 2020 Jul 21;1-36.
doi: 10.1080/22221751.2020.1799723. Online ahead of print.
Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells
Sofia Appelberg[SUP] 1 [/SUP], Soham Gupta[SUP] 2 [/SUP], Sara Svensson Akusj?rvi[SUP] 2 [/SUP], Anoop T Ambikan[SUP] 2 [/SUP], Flora Mikaeloff[SUP] 2 [/SUP], Elisa Saccon[SUP] 2 [/SUP], ?kos V?gv?ri[SUP] 3 [/SUP], Rui Benfeitas[SUP] 4 [/SUP], Maike Sperk[SUP] 2 [/SUP], Marie St?hlberg[SUP] 3 [/SUP], Shuba Krishnan[SUP] 2 [/SUP], Kamal Singh[SUP] 2 5 [/SUP], Josef M Penninger[SUP] 6 7 [/SUP], Ali Mirazimi[SUP] 1 2 8 [/SUP], Ujjwal Neogi[SUP] 2 5 [/SUP]
Affiliations
- PMID: 32691695
- DOI: 10.1080/22221751.2020.1799723
Abstract
How severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections engage cellular host pathways and innate immunity in infected cells remains largely elusive. We performed an integrative proteo-transcriptomics analysis in SARS-CoV-2 infected Huh7 cells to map the cellular response to the invading virus over time. We identified four pathways, ErbB, HIF-1, mTOR and TNF signaling, among others that were markedly modulated during the course of the SARS-CoV-2 infection in vitro. Western blot validation of the downstream effector molecules of these pathways revealed a dose-dependent activation of Akt, mTOR, S6K1 and 4E-BP1 at 24 hours post infection (hpi). However, we found a significant inhibition of HIF-1α through 24hpi and 48hpi of the infection, suggesting a crosstalk between the SARS-CoV-2 and the Akt/mTOR/HIF-1 signaling pathways. Inhibition of the mTOR signaling pathway using Akt inhibitor MK-2206 showed a significant reduction in virus production. Further investigations are required to better understand the molecular sequelae in order to guide potential therapy in the management of severe coronavirus disease 2019 (COVID-19) patients.
Keywords: SARS-CoV-2; mTOR; proteomics; transcriptomics.